Galactocerebroside and glucocerebroside will be the primary topics for study. The lipoproteins of brain that bind galactocerebroside will be characterized, quantified as a function of age and pathology, and their functional roles identified. Further attempts will be made to isolate the enzymes that hydrolyze the two lipids. Additional cerebroside and ceramide analogs will be synthesized and tested for their ability to inhibit or stimulate cerebroside hydrolysis or synthesis. The effects of these compounds will be tested in rats, tissue slices, and cultured cells to see the effects of interfering with cerebroside metabolism. It is possible that we may be able to develop model forms of Gaucher's and Krabbe's diseases, and to ameliorate the disorders by slowing the synthesis of the cerebrosides. The uptake by cells of the cerebrosides will be studied to determine the factors controlling the uptake and to characterize the binding sites in the membranes. BIBLIOGRAPHIC REFERENCE: Synthetic inhibitors of glucocerebroside beta-glucosidase. J.C. Hyun, R.S. Misra, D. Greenblatt, and N.S. Radin. Arch. Biochem. Biophys. 166, 382-389 (1975).